Modular Design of Salmonella Typhimurium OMV-Based Nanovaccines for Tunable Dual-Form Polysaccharide Antigen Delivery

Bacterial diseases are primarily managed with antibiotics, but vaccination is widely acknowledged as the most efficacious strategy for their prevention. Bacterial polysaccharides serve as key protective antigens in hosts and are therefore consistently prioritized as targets for bacterial vaccine development. Polysaccharide-conjugated vaccines have emerged as a promising and effective approach to combat multidrug-resistant bacteria. In order to construct a vaccine carrier capable of delivering bacterial polysaccharides while inducing robust immune response, this study utilized outer membrane vesicles (OMVs) derived from Salmonella Typhimurium as the vaccine carrier instead of the traditional adjuvant components to enhance the immunogenicity of polysaccharide vaccine. S. Typhimurium was genetically engineered to enable the controlled synthesis of LPS and glycoprotein, which were encapsulated within OMVs as two distinct polysaccharide vaccine formulations. This engineered delivery system was used to deliver the O-antigen polysaccharide of Shigella flexneri 3a, and subsequent validation in a murine model further confirmed that its ability to elicit an effective in vivo immune response. The polysaccharide delivery carrier platform established in this study provides a foundation for the subsequent multi-form delivery of bacterial polysaccharides in next-generation biological vaccines.

细菌性疾病的防控主要依赖抗生素，但疫苗接种被广泛公认为是预防此类疾病的最有效策略。细菌多糖是宿主体内关键的保护性抗原，因此始终被列为细菌性疫苗研发的优先靶点。多糖结合疫苗已成为对抗多重耐药菌的极具潜力且高效的技术手段。为构建可递送细菌多糖且能诱导强烈免疫应答的疫苗载体，本研究采用鼠伤寒沙门氏菌（Salmonella Typhimurium）衍生的外膜囊泡（outer membrane vesicles, OMVs）作为疫苗载体，以替代传统佐剂成分，从而提升多糖疫苗的免疫原性。研究人员对该菌株进行基因工程改造，使其能够受控合成脂多糖（Lipopolysaccharide, LPS）与糖蛋白，并将二者作为两种不同的多糖疫苗制剂包裹于外膜囊泡中。本研究利用该工程化递送系统递送福氏志贺菌3a型（Shigella flexneri 3a）的O抗原多糖，随后在小鼠模型中开展的验证实验进一步证实，该系统可诱导有效的体内免疫应答。本研究构建的多糖递送载体平台，为后续在下一代生物疫苗中实现细菌多糖的多形式递送奠定了坚实基础。